Treatment monitoring of immunotherapy and targeted therapy using FET PET in patients with melanoma and lung cancer brain metastases: Initial experiences.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13525-e13525 ◽  
Author(s):  
Norbert Galldiks ◽  
Diana S.Y. Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Treatment Monitoring ◽  
Mri Findings ◽  
Fet Pet

e13525 Background: Due to the lack of specificity of contrast-enhanced (CE) MRI, the differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (IT) or targeted therapy (TT) may be challenging, especially when IT or TT is applied in combination with radiotherapy (RT). Similarly, for response assessment of RT plus IT or targeted therapy (TT), the use of CE MRI alone may also be difficult. For problem solving, the integration of advanced imaging methods may add valuable information. Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) in comparison to CE MRI for these important clinical situations in patients with brain metastases (BM) secondary to malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Methods: From 2015-2018, we retrospectively identified 31 patients with 74 BM secondary to MM (n = 20 with 42 BM) and NSCLC (n = 11 with 32 BM) who underwent 52 FET PET scans during the course of disease. All patients had RT prior to IT or TT initiation (61%) or RT concurrent to IT or TT (39%). In 13 patients, FET PET was performed for treatment response assessment of IT or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET PET was used for the differentiation of progression from PsP related to RT plus IT or TT. In all BM, metabolic activity on FET PET was evaluated by calculation of tumor/brain ratios. FET PET imaging findings were compared to CE MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. Results: In 4 of 13 patients (31%), FET PET provided additional information for treatment response evaluation beyond the information provided by CE MRI alone. Furthermore, responding patients on FET PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE MRI findings suggesting progression, FET PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. Conclusions: FET PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with IT or TT.

scholarly journals OTHR-14. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING FET PET IN PATIENTS WITH MELANOMA AND LUNG CANCER BRAIN METASTASES: INITIAL EXPERIENCES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i21-i21
Author(s):  
Norbert Galldiks ◽  
Diana Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Treatment Monitoring ◽  
Mri Findings ◽  
Fet Pet ◽  
Additional Information

Abstract BACKGROUND: Due to the lack of specificity of contrast-enhanced (CE) MRI, both the response assessment and differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (ICI) or targeted therapy (TT) may be challenging, especially when ICI or TT is applied in combination with radiotherapy (RT). Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) as a problem-solving tool in comparison to CE-MRI in patients with brain metastases (BM) secondary to malignant melanoma (MM) and NSCLC. METHODS: We retrospectively identified 31 patients with 74 BM secondary to MM (n=20 with 42 BM) and NSCLC (n=11 with 32 BM) who underwent 52 FET-PET scans during the course of disease. All patients had RT prior to ICI or TT initiation (61%) or RT concurrent to ICI or TT (39%). In 13 patients, FET-PET was performed for treatment response assessment of ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET-PET was used for the differentiation of progression from PsP related to RT plus ICI or TT. In all BM, metabolic activity on FET-PET was evaluated by calculation of tumor/brain ratios. FET-PET imaging findings were compared to CE-MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. RESULTS: In 4 of 13 patients (31%), FET-PET provided additional information for treatment response evaluation beyond the information provided by CE-MRI alone. Furthermore, responding patients on FET-PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE-MRI findings suggesting progression, FET-PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. CONCLUSIONS: FET-PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with ICI or TT.

scholarly journals 32. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING AMINO ACID PET IN PATIENTS WITH BRAIN METASTASES

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii5-ii6
Author(s):  
Norbert Galldiks ◽  
Diana Abdulla ◽  
Matthias Scheffler ◽  
Fabian Wolpert ◽  
Jan-Michael Werner ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Amino Acid ◽  
Brain Metastases ◽  
Response Assessment ◽  
Diagnostic Value ◽  
Treatment Monitoring ◽  
Fet Pet ◽  
Time To Peak ◽  
Amino Acid Pet

Abstract PURPOSE Recently, the RANO group has analyzed the additional diagnostic value of amino acid PET in patients with primary and secondary brain tumors and recommended the use of this imaging technique in addition to conventional MRI. Here, we investigated the value of PET using the radiolabled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET) for treatment monitoring of immune checkpoint inhibition (ICI) or targeted therapy (TT) alone or in combination with radiotherapy in patients with brain metastases (BM) since contrast-enhanced MRI often remains inconclusive. METHODS We retrospectively identified 40 patients with 107 BM secondary to melanoma (n=29 with 75 BM) or non-small cell lung cancer (n=11 with 32 BM) treated with ICI or TT who had FET PET (n=60 scans) for treatment monitoring from 2015–2019. The majority of patients (n=37; 92.5%) had radiotherapy during the course of disease. In 27 patients, FET PET was used for the differentiation of treatment-related changes from BM relapse following ICI or TT. In 13 patients, FET PET was performed for response assessment to ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In all lesions, static and dynamic FET PET parameters were obtained (i.e., mean tumour-to-brain ratios (TBR), time-to-peak values). Diagnostic accuracies of PET parameters were evaluated by receiver-operating-characteristic analyses using the clinical follow-up or neuropathological findings as reference. RESULTS A TBR threshold of 1.95 differentiated BM relapse from treatment-related changes with an accuracy of 85% (P=0.003). Metabolic Responders to ICI or TT on FET PET had a significantly longer stable follow-up (threshold of TBR reduction relative to baseline, ≥10%; accuracy, 82%; P=0.004). Furthermore, at follow-up, time-to-peak values in metabolic responders increased significantly (P=0.019). CONCLUSIONS FET PET may add valuable information for treatment monitoring in BM patients treated with ICI or TT.

scholarly journals Treatment Monitoring of Immunotherapy and Targeted Therapy using 18F-FET PET in Patients with Melanoma and Lung Cancer Brain Metastases: Initial Experiences

2020 ◽  
pp. jnumed.120.248278
Author(s):  
Norbert Galldiks ◽  
Diana SY Abdulla ◽  
Matthias Scheffler ◽  
Fabian Wolpert ◽  
Jan-Michael Werner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Monitoring ◽  
Fet Pet

OS03.3.A Characterization of long-term metabolic changes of irradiated brain metastases using serial dynamic FET PET imaging

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
N Galldiks ◽  
G Stoffels ◽  
J Werner ◽  
E K Bauer ◽  
C Baues ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Mri Findings ◽  
Fet Pet ◽  
Radiation Induced ◽  
Induced Changes ◽  
Pet Scans ◽  
Dynamic Fet Pet

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. MATERIAL AND METHODS From 2010–2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2–6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2–64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5–60 months). The overall median follow-up time was 26 months (range, 8–101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P<0.001). CONCLUSION FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.

NIMG-06. CHARACTERIZATION OF LONG-TERM METABOLIC CHANGES OF IRRADIATED BRAIN METASTASES USING SERIAL DYNAMIC FET PET IMAGING

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi128-vi128
Author(s):  
Norbert Galldiks ◽  
Gabriele Stoffels ◽  
Jan Werner ◽  
Elena Bauer ◽  
Christian Baues ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Mri Findings ◽  
Fet Pet ◽  
Radiation Induced ◽  
Induced Changes ◽  
Pet Scans ◽  
Dynamic Fet Pet

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. PATIENTS AND METHODS From 2010-2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2-6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2-64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5-60 months). The overall median follow-up time was 26 months (range, 8-101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P< 0.001). CONCLUSIONS FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.

scholarly journals Delayed contrast and multiparametric MRI for treatment response assessment in brain metastases following stereotactic radiosurgery

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv22-iv23
Author(s):  
Markand Patel ◽  
Dilina Rajapakse ◽  
Jian Ping Jen ◽  
Sara Meade ◽  
Helen Benghiat ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Treatment Response ◽  
Sensitivity And Specificity ◽  
Neuroendocrine Tumour ◽  
Response Assessment ◽  
Multiparametric Mri ◽  
Treatment Response Assessment ◽  
Measuring Signal

Abstract Aims Following stereotactic radiosurgery (SRS), brain metastases can increase in size in up to a third of cases. Conventional magnetic resonance imaging (MRI) has a limited role to distinguish between tumour recurrence and SRS-induced changes, which can impact patient management. Delayed contrast MRI treatment response assessment maps (TRAM) use the principle of contrast clearance seen in other tumours, where high vascularity shows a rapid rise in contrast as well as rapid clearance, whereas areas of damaged or low vascularity show accumulation of contrast. We aimed to assess the ability of delayed contrast MRI and multiparametric MRI techniques of diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) to distinguish between radiation-related effects and tumour tissue, as these techniques assess tissue physiological and metabolic information. Method A retrospective review was performed on 23 patients who had delayed contrast and multiparametric MRI between October 2018 to April 2020. Studies were restricted to cases with brain metastases enlarging post-SRS with uncertainty at the MDT meeting regarding progression or treatment-related change, impacting the patient’s management. MRI was performed at 3T including DWI, PWI, MRS with short and intermediate echo times, and 3D T1 MPRAGE at 3-5, 20-30 and 70-90 minutes after administration of intravenous contrast. Contrast clearance analysis was performed by selecting an enhancing region of interest (ROI), measuring signal intensities at the three different timepoints and taking apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) values from the ROI. Choline/Creatine values were calculated from a single-voxel (10 mm isotropic) encompassing the entire contrast-enhancing lesion. Outcome was established from MRI follow-up at 6 months, with a stable or responding lesion considered treatment-related changes and increase considered progression. Results Across 23 patients, 24 metastases were assessed. Two patients were excluded as appropriate follow-up was not available. Sites of primary tumours included breast (n=8), lung (n=6), melanoma (n=4), neuroendocrine tumour from the lung (n=2) and renal cell carcinoma (n=2). Mean age was 56 years and 50% were female. In this cohort, 59% (n=13) were classified as having radiation-related changes on follow-up. Delayed MRI contrast clearance between the 3-5 and 70-90 minute imaging was significantly higher in cases of progression (23.6% vs. 2.5% decrease, p<0.05), as were the rCBV and Cho/Cr ratio (rCBV 3.1 vs. 1.5 and Cho/Cr ratio 2.3 vs. 1.4, p<0.05). Accuracy, sensitivity and specificity of using TRAM alone (contrast clearance decrease of >0%) for progression was 63%/100%/38%, PWI alone (rCBV cut-off 2.0) yielded results of 77%/75%/79% and for both Cho/Cr ratio alone (cut-off 1.8) and combined with TRAM, it was 90%/88%/92%. Neuroradiologist assessment of all techniques was 95%/100%/92%. Conclusion This study shows the effectiveness of delayed contrast and multiparametric MRI for treatment response assessment in patients with brain metastases treated by SRS in clinical practice. Although a delayed contrast MRI study is a very sensitive tool for detecting tumour progression, it lacks specificity. The accuracy of differentiating between tumour and treatment-related effects increases when delayed contrast MRI is used in combination with other advanced techniques such as MRS. By combining all these techniques, neuroradiologists had the highest accuracy, sensitivity and specificity for detecting progression in post-SRS brain metastases.

scholarly journals Feasibility of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for treatment monitoring of brain metastases in lung cancer patients

2019 ◽  
Vol 30 ◽  
pp. ii64-ii65
Author(s):  
D.S. Abdulla ◽  
M. Ruge ◽  
M. Scheffler ◽  
L. Nogova ◽  
S. Koleczko ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Treatment Monitoring ◽  
Fet Pet ◽  
Lung Cancer Patients

The Value of FDG PET/CT in Treatment Response Assessment, Follow-Up, and Surveillance of Lung Cancer

2017 ◽  
Vol 208 (2) ◽  
pp. 420-433 ◽  
Author(s):  
Sara Sheikhbahaei ◽  
Esther Mena ◽  
Anusha Yanamadala ◽  
Siddaling Reddy ◽  
Lilja B. Solnes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Treatment Response ◽  
Fdg Pet ◽  
Response Assessment ◽  
Pet Ct ◽  
Treatment Response Assessment ◽  
Fdg Pet Ct

scholarly journals Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression

2019 ◽  
Vol 22 (1) ◽  
pp. 17-30 ◽  
Author(s):  
Norbert Galldiks ◽  
Martin Kocher ◽  
Garry Ceccon ◽  
Jan-Michael Werner ◽  
Anna Brunn ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Additional Information ◽  
Contrast Enhanced ◽  
Amino Acid Pet ◽  
Cancer Types ◽  
Induced Changes

Abstract The advent of immunotherapy using immune checkpoint inhibitors (ICIs) and targeted therapy (TT) has dramatically improved the prognosis of various cancer types. However, following ICI therapy or TT—either alone (especially ICI) or in combination with radiotherapy—imaging findings on anatomical contrast-enhanced MRI can be unpredictable and highly variable, and are often difficult to interpret regarding treatment response and outcome. This review aims at summarizing the imaging challenges related to TT and ICI monotherapy as well as combined with radiotherapy in patients with brain metastases, and to give an overview on advanced imaging techniques which potentially overcome some of these imaging challenges. Currently, major evidence suggests that imaging parameters especially derived from amino acid PET, perfusion-/diffusion-weighted MRI, or MR spectroscopy may provide valuable additional information for the differentiation of treatment-induced changes from brain metastases recurrence and the evaluation of treatment response.

scholarly journals Correlation of Clinical Parameters with Intracranial Outcome in Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Pd-1/Pd-L1 Inhibitors as Monotherapy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1562
Author(s):  
Konstantinos Rounis ◽  
Marcus Skribek ◽  
Dimitrios Makrakis ◽  
Luigi De Petris ◽  
Sofia Agelaki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Response Assessment ◽  
Small Cell ◽  
University Hospital ◽  
Response Analysis ◽  
Small Cell Lung

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.

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